MHGTMDA: Molecular heterogeneous graph transformer based on biological entity graph for miRNA-disease associations prediction.

MicroRNAs (miRNAs) play a crucial role in the prevention, prognosis, diagnosis, and treatment of complex diseases. Existing computational methods primarily focus on biologically relevant molecules directly associated with miRNA or disease, overlooking the fact that the human body is a highly complex system where miRNA or disease may indirectly correlate with various types of biomolecules. To address this, we propose a novel prediction model named MHGTMDA (miRNA and disease association prediction using heterogeneous graph transformer based on molecular heterogeneous graph). MHGTMDA integrates biological entity relationships of eight biomolecules, constructing a relatively comprehensive heterogeneous biological entity graph. MHGTMDA serves as a powerful molecular heterogeneity map transformer, capturing structural elements and properties of miRNAs and diseases, revealing potential associations. In a 5-fold cross-validation study, MHGTMDA achieved an area under the receiver operating characteristic curve of 0.9569, surpassing state-of-the-art methods by at least 3%. Feature ablation experiments suggest that considering features among multiple biomolecules is more effective in uncovering miRNA-disease correlations. Furthermore, we conducted differential expression analyses on breast cancer and lung cancer, using MHGTMDA to further validate differentially expressed miRNAs. The results demonstrate MHGTMDA's capability to identify novel MDAs.